Dr. James Lewis is Associate Professor of Medicine and Epidemiology at the University of Pennsylvania, where he has been actively involved in patient-oriented research related to inflammatory bowel diseases and medication safety. The major theme of his work has been to assess the safety of medications used in the treatment of inflammatory bowel diseases and to improve the therapeutic strategies for these patients. The new science proposed in this application includes a randomized controlled trial for patients with clinically quiescent ulcerative colitis. The proposed study will test whether increasing mesalamine dose can reduce fecal calprotectin (FCP) levels, a marker of intestinal inflammation that is highly predictive of the risk of relapse among patients with quiescent ulcerative colitis. Sixty patients with quiescent ulcerative colitis and elevated FCP levels will be randomized to either increase their mesalamine dose by 2gm per day or to maintain their current dose. FCP will be measured again after 6 weeks (the primary endpoint). Reduction in FCP levels below 50mcg/gm stool at 6 weeks will be the primary outcome. The proportion of patients achieving this outcome will be compared between groups using Fisher's exact test. After 6 weeks, all patients will be treated with mesalamine at a dose 2gm higher than that prescribed immediately prior to randomization (i.e. the control arm will cross-over into the experimental arm). FCP will be measured again at week 12. All randomized patients as well as those who were excluded from the randomized trial because of a low FCP concentration at baseline will be followed to week 48 to determine the rate of clinical relapse. During the period of funding for the K24, Dr. Lewis will continue to serve as primary mentor for gastroenterology fellows, junior faculty, residents and medical students interested in patient oriented research. In addition, during the period of the award, Dr. Lewis will serve as the director of the Clinical Trials track within the University's Master of Science in Clinical Epidemiology Program, thereby allowing him to further expand his mentoring role. This K24 award will be essential to allow Dr. Lewis sufficient protected time from clinical activities to continue to develop his research program and mementoring activities.